62718-31-4

Step 1 Preparation of intermediate 1-benzyl-4-carbonylamide piperidine

To piperidine-4-carboxamide (16.5 g, 0.13 mol ) and K₂CO₃ (35.6 g, 0.26 mol) in EtOH (350 ml) was added benzyl bromide (22.0 g, 0.13 mol) And heated to reflux for 3 h, cooled to room temperature and filtered. The filtrate was evaporated in vacuo and H₂O (200ml) was added. The aqueous layer was extracted with CH₂Cl₂ (3×150ml), the organic layers were combined, and Na₂SO₄Dry and filter. The solvent was evaporated in vacuo to give the product as a white solid (20.0 g, 71.0%).

Step 2 Preparation of intermediate 1-benzyl-4-cyanopiperidine

1-benzyl-4-carbonylamide piperidine (20.0 g, 91.7 mmol) Mixed with P₂O₅ (16.92, 119.2 mmol) and heated under argon at 180-200°C for 3 h, cooled to room temperature and added H₂O (150 ml). The aqueous solution was basified by the careful addition of K₂CO₃ and then extracted with EtOAc (3× 150 ml). The organic extract was dried over Na₂SO₄, filtered and the solvent evaporated in vacuo to give a yellow oil (16.7 g, 90.9%).